EXPRESSION OF I-MU - C-GAMMA HYBRID GERMLINE TRANSCRIPTS SUBSEQUENT TO IMMUNOGLOBULIN HEAVY-CHAIN CLASS SWITCHING

Germline C-H transcripts initiate from a non-coding I exon and terminate downstream of the associated C-H exons. Ig heavy chain class switch recombination from the VDJ - C-mu gene to particular downstream C-H genes appears to be regulated by a process that involves mitogen and/or cytokine induction of germline C-H transcripts from the downstream genes. We have examined the expression of germline C-mu transcripts (I-mu,- C-mu, transcripts) in splenic B cells and pre-a cell lines after cytokine and mitogen stimulation. In contrast to the expression of the germline transcripts from downstream C-H genes, expression of germline C-mu transcripts was constitutive and unaffected by mitogen and cytokine treatment. After a primary switch recombination event, the germline I-mu promoter, which is now associated with a downstream C-H gene, continues to be active-leading to the generation of a novel germline transcript consisting of the I-mu exon spliced to the C-H exons of the switched C-H gene. We discuss the potential role of the expression of hybrid I-mu-containing transcripts in the class switch process. We also describe a novel and sensitive assay, based on the detection of the hybrid I-mu-containing transcripts, that allows detection of class switch recombination events even in heterogeneous populations of cells.